| Structural highlights
Function
[MX2_HUMAN] Interferon-induced dynamin-like GTPase with potent antiviral activity against human immunodeficiency virus type 1 (HIV-1). Acts by targeting the viral capsid and affects the nuclear uptake and/or stability of the HIV-1 replication complex and the subsequent chromosomal integration of the proviral DNA. Exhibits antiviral activity also against simian immunodeficiency virus (SIV-mnd). May play a role in regulating nucleocytoplasmic transport and cell-cycle progression.[1] [2] [3] [4]
Publication Abstract from PubMed
Human dynamin-like, interferon-induced myxovirus resistance 2 (Mx2 or MxB) is a potent HIV-1 inhibitor. Antiviral activity requires both the amino-terminal region of MxB and protein oligomerization, each of which has eluded structural determination due to difficulties in protein preparation. We report that maltose binding protein-fused, full-length wild-type MxB purifies as oligomers and further self-assembles into helical arrays in physiological salt. Guanosine triphosphate (GTP), but not guanosine diphosphate, binding results in array disassembly, whereas subsequent GTP hydrolysis allows its reformation. Using cryo-electron microscopy (cryoEM), we determined the MxB assembly structure at 4.6 A resolution, representing the first near-atomic resolution structure in the mammalian dynamin superfamily. The structure revealed previously described and novel MxB assembly interfaces. Mutational analyses demonstrated a critical role for one of the novel interfaces in HIV-1 restriction.
CryoEM structure of MxB reveals a novel oligomerization interface critical for HIV restriction.,Alvarez FJD, He S, Perilla JR, Jang S, Schulten K, Engelman AN, Scheres SHW, Zhang P Sci Adv. 2017 Sep 15;3(9):e1701264. doi: 10.1126/sciadv.1701264. eCollection 2017, Sep. PMID:28929138[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ King MC, Raposo G, Lemmon MA. Inhibition of nuclear import and cell-cycle progression by mutated forms of the dynamin-like GTPase MxB. Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8957-62. Epub 2004 Jun 7. PMID:15184662 doi:http://dx.doi.org/10.1073/pnas.0403167101
- ↑ Goujon C, Moncorge O, Bauby H, Doyle T, Ward CC, Schaller T, Hue S, Barclay WS, Schulz R, Malim MH. Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection. Nature. 2013 Oct 24;502(7472):559-62. doi: 10.1038/nature12542. Epub 2013 Sep 18. PMID:24048477 doi:http://dx.doi.org/10.1038/nature12542
- ↑ Liu Z, Pan Q, Ding S, Qian J, Xu F, Zhou J, Cen S, Guo F, Liang C. The interferon-inducible MxB protein inhibits HIV-1 infection. Cell Host Microbe. 2013 Oct 16;14(4):398-410. doi: 10.1016/j.chom.2013.08.015., Epub 2013 Sep 19. PMID:24055605 doi:http://dx.doi.org/10.1016/j.chom.2013.08.015
- ↑ Kane M, Yadav SS, Bitzegeio J, Kutluay SB, Zang T, Wilson SJ, Schoggins JW, Rice CM, Yamashita M, Hatziioannou T, Bieniasz PD. MX2 is an interferon-induced inhibitor of HIV-1 infection. Nature. 2013 Oct 24;502(7472):563-6. doi: 10.1038/nature12653. Epub 2013 Oct 13. PMID:24121441 doi:http://dx.doi.org/10.1038/nature12653
- ↑ Alvarez FJD, He S, Perilla JR, Jang S, Schulten K, Engelman AN, Scheres SHW, Zhang P. CryoEM structure of MxB reveals a novel oligomerization interface critical for HIV restriction. Sci Adv. 2017 Sep 15;3(9):e1701264. doi: 10.1126/sciadv.1701264. eCollection 2017, Sep. PMID:28929138 doi:http://dx.doi.org/10.1126/sciadv.1701264
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